Dronedarone is a benzofuran derivative; it works as a multichannel blocker, inhibiting potassium currents and thereby prolonging the cardiac action potential and refractory periods. It also inhibits sodium and calcium currents and non-competitively antagonises adrenergic activities.1
The ATHENA study, a randomised double-blind trial in 4628 patients with AF/atrial flutter and at least one additional risk factor for death, compared hospitalisation due to cardiovascular events or death rate of patients receiving dronedarone 400mg twice daily versus placebo. After a mean follow-up period of 21 months, patients on dronedarone were less likely to be hospitalised or die than those receiving placebo (39.4% versus 31.9%, p<0.001). First hospitalisation due to cardiovascular events was seen in 29.3% of the dronedarone group compared with 36.9 per cent in the placebo group (p<0.001). Patients on dronedarone were less likely to die from cardiovascular causes than those receiving placebo (2.7% versus 3.9%, p=0.03); all cause mortality rates were 5.0% in the dronedarone group and 6.0% in the placebo group (p=0.18).2
A post hoc analysis of the same study found that the use of dronedarone versus placebo reduced the risk of stroke from 1.8% to 1.2% per year (p=0.027). This effect was observed regardless of whether patients were taking oral anticoagulants.3
Two identical randomised, double-blind studies, one carried out in Europe and the other outside Europe (EURIDIS and ADONIS), compared the efficacy of dronedarone to placebo in maintaining sinus rhythm in patients with paroxysmal or persistent atrial fibrillation/atrial flutter. Dronedarone reduced the risk of AF recurrence within the first year from 75.2% with placebo to 64.1% (relative risk reduction 25 per cent; p<0.001).4 The median time to first recurrence of AF was increased in the dronedarone group compared to placebo (116 days versus 53 days).4 When patients with AF alone were analysed, the median time to first confirmed AF recurrence was 46 days in the placebo group (n=354) compared to 92 days in patients receiving dronedarone 400mg twice daily (n=727). The relative risk of AF recurrence within 12 months was 22% lower in the dronedarone group than in the placebo group (p=0.0015).5 Dronedarone decreased the mean ventricular rate on first recurrence from 116.4bpm with placebo to 102.5bpm (p<0.0001).6
The adverse effects most frequently associated with dronedarone are diarrhoea, nausea and vomiting, fatigue and asthenia.1 In clinical trials, rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in patients who received dronedarone compared to placebo.2,4
- Multaq Summary of product characteristics, 2009.
- Hohnloser SH et al. N Engl J Med 2009; 360: 668-78.
- Connolly SJ et al. Circulation 2009; 120: 1174-80.
- Singh BN et al. N Engl J Med 2007: 357; 987-99.
- DOF-EURIDIS/ADONIS Pooled AF only data: Time to first recurrence.
- DOF-EURIDIS/ADONIS Pooled AF only data: Ventricular rate control.
Further information: sanofi-aventis
Updated 26 August 2010
NICE has approved dronedarone (Multaq) as a second-line treatment for certain patients with atrial fibrillation.
Dronedarone (Multaq) blocks multiple ion channels, lowering ventricular rate and preventing recurrence of atrial fibrillation.
The institute revised its original plan to reject dronedarone following a campaign by patients, healthcare professionals and MPs.